title: A possible role of HMGB1 in DNA demethylation in CD4+ T cells from patients with systemic lupus erythematosus.
abstract: The aberrant activity of CD4(+) T cells in patients with systemic lupus erythematosus (SLE) is associated with DNA hypomethylation of the regulatory regions in CD11a and CD70 genes. Our previous studies demonstrated that Gadd45a contributes to the development of SLE by promoting DNA demethylation in CD4(+) T cells. In this study, we identified proteins that bind to Gadd45a in CD4(+) T cells during SLE flare by using the method of co-immunoprecipitation and mass spectrometry, High mobility group box protein 1 (HMGB1) is one of identified proteins. Furthermore, gene and protein expression of HMGB1 was significantly increased in SLE CD4(+) T cells compared to controls, and HMGB1 mRNA was correlated with CD11a and CD70 mRNA. A significant, positive correlation was found between HMGB1 mRNA and SLEDAI for SLE patients. Our data demonstrate that HMGB1 binds to Gadd45a and may be involved in DNA demethylation in CD4(+) T cells during lupus flare.
authors.affiliation: Department of Dermatology and Epigenetic Research Center, Key Laboratory of Diabetes Immunology of Ministry of Education, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.forename: Chenghui
authors.initials: C
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Gongping
authors.initials: G
authors.lastname: Liang
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Susan
authors.initials: S
authors.lastname: Yung
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D024243:HMGB1 Protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; C439070:GADD45A protein, human; D000097642:GADD45 Proteins